The FDA approval of Keytruda this month may help some patients in their battle against asbestos cancer.
Keytruda is the brand name for the immunotherapy drug pembrolizumab. The FDA first approved Keytruda as a first-line treatment for metastatic non-small cell lung cancer. That initial approval came in 2017.
The new FDA approval of Keytruda is for treatment of specific kinds of malignant tumors. Eligible patients must have unresectable mesothelioma and no other treatment options.
How Keytruda Fights Mesothelioma
Keytruda is an immune checkpoint inhibitor. It blocks a protein called PD-L1. Mesothelioma cells use PD-L1 to avoid immune system attack. Drugs like Keytruda unmask these hiding cells and make them more vulnerable to treatment.
But not all patients with mesothelioma will benefit from the most recent FDA approval of Keytruda. That is because only a small percentage of mesothelioma patients overexpress PD-L1. Previous studies suggest that fewer than one in five mesothelioma patients have high enough levels of PD-L1 to make pembrolizumab effective.
These patients stand to gain the most from the FDA approval of Keytruda. The FDA specified that the latest approval covers patients with a high tumor mutational burden (TMB-H). In mesothelioma, high PD-L1 is the reason for high tumor mutational burden.
Study Results Led to FDA Approval of Keytruda
The FDA based its approval of Keytruda for mesothelioma on a clinical trial that is still going on. The KEYNOTE-158 trial divided cancer patients into two groups. One group had a high tumor mutational burden. The other group did not. Patients received 200 mg of Keytruda every three weeks.
Only a small number of mesothelioma patients fit into the TMB-H group. But these patients had the best responses. FDA approval of Keytruda reflects the fact that twenty-nine percent of the TMB-H patients responded to the treatment. Only six percent of those with low mutational burden responded.
At one year, more than 26 percent of TMB-H group members still did not have cancer progression. Only 14 percent of the non-TMB-H group made it this long without tumor growth.
“I believe the FDA made the right decision to approve pembrolizumab based on these findings,” KEYNOTE-158 investigator Marwan G. Fakih, MD, told Targeted Oncology. “However, much still needs to be learned regarding the extent of benefit within each of these tumor types and others.”
In spite of the FDA approval of Keytruda, it is not a miracle drug for mesothelioma. The 2019 PROMISE trial showed mesothelioma patients on Keytruda died a little sooner than those on standard chemotherapy.
Pebrolizumab in Combination with Other Treatments
Mesothelioma doctors have seen better results by combining Keytruda with other therapies. Several ongoing clinical trials use Keytruda along with chemotherapy, surgery, or even other immunotherapy drugs.
The FDA approval of Keytruda marks only the second time they have approved a medication for this disease. The first mesothelioma drug was Alimta. It won FDA approval in 2004. It is still the primary chemotherapy drug for mesothelioma.
Last year, the FDA also approved Tumor Treating Fields (now called Optune Lua) for pleural mesothelioma. This non-drug treatment aims to shrink mesothelioma tumors with electricity.
Astor, Lisa, “FDA Approves Pembrolizumab for TMB-High Solid Tumors”, June 16, 2020, https://www.targetedonc.com/view/fda-approves-pembrolizumab-for-tmb-high-solid-tumors
“FDA approves pembrolizumab for adults and children with TMB-H solid tumors”, June 17, 2020, FDA website, https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors